G Protein-Coupled Receptor Pharmacology-Insights from Mass Spectrometry

We describe the utility of MS, including HDX-MS and native-MS, in investigating GPCR pharmacology. Specifically, we include ligand-drug interactions and Gi/s protein coupling and illustrate how these techniques can lead to the discovery of endogenous allosteric ligands and thereby offer a new perspective for drug discovery of GPCRs. SIGNIFICANCE STATEMENT: GPCRs are the largest and most diverse group of membrane receptors in eukaryotes. To carry out signaling, GPCRs adopt a range of conformational states to elicit G-protein coupling or arrestin binding. Because of their conformational dynamics, GPCRs remain challenging to study, particular in the gas phase after release from their protective detergent micelles. Over the past decade great advances have been made, however, enabling direct measure of coupling and signaling across native membranes. In this review we highlight these advances and consider the future of this exciting and challenging area.PMID:36918259 | DOI:10.1124/pharmrev.120.000237
Source: Pharmacognosy Reviews - Category: Drugs & Pharmacology Authors: Source Type: research